Transgenic mice depleted in mature t-cells and methods for making transgenic mice

Abstract

Transgenic mice having a phenotype characterized by the substantial absence of mature T lymphocytes otherwise naturally occurring in said mice. The phenotype is conferred in the transgenic mouse by a transgene contained in at least the precursor stem cell of the T lymphocyte which is depleted. The transgene comprises a DNA sequence encoding a T cell receptor polypeptide variant which inhibits maturation of the T lymphocyte.

What is claimed is: 
     
       1. A transgenic mouse having a phenotype characterized by the substantial absence of mature T-cells otherwise naturally occurring in said mouse, said phenotype being conferred by a transgene contained in the somatic and germ cells of said mouse, said transgene comprising the ΔV-TCRβ DNA fragment which encodes a T-cell antigen receptor polypeptide variant, and said polypeptide variant being incapable of mediating T-cell maturation in said transgenic mouse. 
     
     
       2. A method for producing a transgenic mouse having a phenotype characterized by the substantial absence of mature T-cells otherwise naturally occurring in said mouse, said method comprising: (a) introducing a transgene into a zygote of a mouse, said transgene comprising the ΔV-TCRβ DNA fragment which encodes a T-cell antigen receptor polypeptide variant, said polypeptide variant being incapable of mediating T-cell maturation in said transgenic mouse,   (b) transplanting said zygote into a pseudopregnant mouse.   (c) allowing said zygote to develop to term, and   (d) identifying at least one transgenic offspring containing said transgene.   
     
     
       3. A method for producing a transgenic mouse having a phenotype characterized by the substantial absence of mature T-cells otherwise naturally occurring in said mouse, said method comprising: (a) introducing a transgene into an embryo of a mouse, said transgene comprising the ΔV-TCRβ DNA fragment which encodes a T-cell antigen receptor polypeptide variant, said polypeptide variant being incapable of mediating T-cell maturation in said transgenic mouse.   (b) transplanting said embryo into a pseudopregnant mouse,   (c) allowing said embryo to develop to term, and   (d) identifying at least one transgenic offspring containing said transgene, and   (e) breeding said offspring to form a transgenic mouse having said phenotype.   
     
     
       4. The method of claim 3 wherein said introducing of said transgene into said embryo is by introducing an embryonic stem cell containing said transgene into said embryo. 
     
     
       5. The method of claim 3 wherein said introducing of said transgene into said embryo is by infecting said embryo with a retrovirus containing said transgene.